Naturally occurring Staphylococcal protein A forms a three-helix structure that bind to the Fc region of IgG. The Z domain of the 58-residue polypeptide derived from the B domain of staphylococcal protein A retains binding.
Affibodies, derived from the Z-domain of protein A, contain a scaffold that are three α-helices connected by loops, where all three helices are required for binding to any other molecule, and 13 amino acids are mutated in the helical segment to provide diversity of binding against targets. Sequence and binding data on a number of affibodies document that 13 sites on these helices can tolerate mutation to any amino acid and maintain binding activity to a target.